Evidence map›Paper›PMID 41592073›Full record

ArticlePLoS biology2026

The lipid-metabolic enzyme HSD17B12 drives lysosomal degradation of PD-L1 potentiating anti-tumor immunity in a mouse model.

Zhihui Zhou, Ying Lu, Pan Li, Xin Liu, Wei Cheng, Hai-Ning Chen, Lunzhi Dai, Haiyan Ren

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in PLoS biology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors.

Zhihui ZhouDepartment of Pulmonary and Critical Care Medicine, Respiratory Infection and Intervention Laboratory of Frontiers Science Center for Disease-related Molecular Network, and State Key Laboratory of Biotherapy, West China Hospital of Sichuan University, Chengdu, Sichuan, China.
Ying LuNational Clinical Research Center for Geriatrics, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
Pan LiDepartment of Pulmonary and Critical Care Medicine, Respiratory Infection and Intervention Laboratory of Frontiers Science Center for Disease-related Molecular Network, and State Key Laboratory of Biotherapy, West China Hospital of Sichuan University, Chengdu, Sichuan, China.
Xin LiuDepartment of Pulmonary and Critical Care Medicine, Respiratory Infection and Intervention Laboratory of Frontiers Science Center for Disease-related Molecular Network, and State Key Laboratory of Biotherapy, West China Hospital of Sichuan University, Chengdu, Sichuan, China.
Wei ChengDepartment of Pulmonary and Critical Care Medicine, Respiratory Infection and Intervention Laboratory of Frontiers Science Center for Disease-related Molecular Network, and State Key Laboratory of Biotherapy, West China Hospital of Sichuan University, Chengdu, Sichuan, China.
Hai-Ning ChenColorectal Cancer Center, Department of General Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
Lunzhi DaiNational Clinical Research Center for Geriatrics, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan, China.ORCID https://orcid.org/0000-0002-3003-8910
Haiyan RenDepartment of Pulmonary and Critical Care Medicine, Respiratory Infection and Intervention Laboratory of Frontiers Science Center for Disease-related Molecular Network, and State Key Laboratory of Biotherapy, West China Hospital of Sichuan University, Chengdu, Sichuan, China.ORCID https://orcid.org/0000-0001-9995-3255

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The high prevalence of cancer immunotherapy resistance, coupled with substantial tumor heterogeneity, underscores the urgent need for innovative therapeutic targets. A deeper understanding of immunoregulatory mechanisms would provide new targets and combination therapeutic strategies for tumor therapy. In this study, we demonstrate that HSD17B12 enhances anti-tumor immunity and represents a promising therapeutic target. Mechanistically, HSD17B12 promotes lysosome-dependent degradation of PD-L1 via the VAC14 and ESCRT complexes across various malignancies, regardless of its 3-ketoacyl-CoA reductase activity. HSD17B12-deficient cells displayed PD-L1 accumulation in both tumor cells and exosomes, reducing T cell-mediated cytotoxicity. Notably, we found a significant negative correlation between HSD17B12 and PD-L1 expression in colorectal cancer tissues. Furthermore, high HSD17B12 expression in CRC correlated with increased infiltration of cytotoxic T cells. Based on these findings, we designed a peptide, HSD-CC1-NPGY, which effectively reduces PD-L1 expression in cells and suppresses tumor growth in a mouse model. Overall, our results establish HSD17B12 as an important regulator of anti-tumor immunity and a promising therapeutic target for cancer treatment.

Indexed as

B7-H1 AntigenColorectal NeoplasmsEstradiol DehydrogenasesLysosomesAnimalsCell Line, TumorDisease Models, AnimalEndosomal Sorting Complexes Required for TransportFemaleHumansLipid MetabolismMiceMice, Inbred C57BLB7-H1 AntigenEndosomal Sorting Complexes Required for TransportEstradiol Dehydrogenases

Identifiers

PMID41592073
PMCPMC12843542

What OpenQuestion holds

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LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.